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Induction of macrophage nitric oxide production by interferon-gamma and tumor necrosis factor-alpha is enhanced by interleukin-10.

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Bibliographic Details
Title: Induction of macrophage nitric oxide production by interferon-gamma and tumor necrosis factor-alpha is enhanced by interleukin-10.
Authors: Corradin, S.B., Fasel, N., Buchmüller-Rouiller, Y., Ransijn, A., Smith, J., Mauël, J.
Publication Year: 2025
Collection: Université de Lausanne (UNIL): Serval - Serveur académique lausannois
Subject Terms: Amino Acid Oxidoreductases/genetics, Animals, Interferon-gamma/pharmacology, Interleukin-10/pharmacology, Lipopolysaccharides/pharmacology, Macrophages/metabolism, Mice, Inbred C3H, Inbred CBA, Nitric Oxide/metabolism, Nitric Oxide Synthase, Nitrites/metabolism, RNA, Messenger/analysis, Recombinant Proteins/pharmacology, Tumor Necrosis Factor-alpha/pharmacology
Description: Interleukin-10 (IL-10) has been reported to inhibit nitric oxide (NO) synthesis and microbicidal activity of interferon-gamma (IFN-gamma)-stimulated macrophages (M phi) by preventing the secretion of tumor necrosis factor-alpha (TNF-alpha) which serves as an autocrine activating signal. We have examined the effects of recombinant IL-10 on the capacity of IFN-gamma together with exogenous TNF-alpha to induce NO synthesis by bone marrow-derived M phi. Under these conditions and in contrast to its reported deactivating potential, IL-10 strongly enhanced NO synthesis measured as nitrite (NO2-) release (half maximal stimulation at approximately 10 U/ml). IL-10 further increased NO2- production by M phi stimulated in the presence of optimal concentrations of prostaglandin E2, a positive modulator of M phi activation by IFN-gamma/TNF-alpha. Increased steady state levels of NO synthase mRNA were observed in 4-h IFN-gamma/TNF-alpha cultures and enhanced NO2(-)-release was evident 24 h but not 48 h after stimulation. These results suggest that the effects of IL-10 on M phi function are more complex than previously recognized.
Document Type: article in journal/newspaper
Language: English
ISSN: 0014-2980
Relation: European Journal of Immunology; https://iris.unil.ch/handle/iris/134685; serval:BIB_A4D61B1FF36D; A1993LT24100050; 7688311
DOI: 10.1002/eji.1830230851
Availability: https://iris.unil.ch/handle/iris/134685
https://doi.org/10.1002/eji.1830230851
Accession Number: edsbas.77DA09E2
Database: BASE
Description
Abstract:Interleukin-10 (IL-10) has been reported to inhibit nitric oxide (NO) synthesis and microbicidal activity of interferon-gamma (IFN-gamma)-stimulated macrophages (M phi) by preventing the secretion of tumor necrosis factor-alpha (TNF-alpha) which serves as an autocrine activating signal. We have examined the effects of recombinant IL-10 on the capacity of IFN-gamma together with exogenous TNF-alpha to induce NO synthesis by bone marrow-derived M phi. Under these conditions and in contrast to its reported deactivating potential, IL-10 strongly enhanced NO synthesis measured as nitrite (NO2-) release (half maximal stimulation at approximately 10 U/ml). IL-10 further increased NO2- production by M phi stimulated in the presence of optimal concentrations of prostaglandin E2, a positive modulator of M phi activation by IFN-gamma/TNF-alpha. Increased steady state levels of NO synthase mRNA were observed in 4-h IFN-gamma/TNF-alpha cultures and enhanced NO2(-)-release was evident 24 h but not 48 h after stimulation. These results suggest that the effects of IL-10 on M phi function are more complex than previously recognized.
ISSN:00142980
DOI:10.1002/eji.1830230851